Delivery of TGFβ3 from Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro

• Published in: Advanced biology 2024-10, Vol.8 (10), p.e2300531-n/a
• Main Authors: Funnell, Jessica L., Fougere, Jasper, Zahn, Diana, Dutz, Silvio, Gilbert, Ryan J.
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - metabolism; Cells, Cultured; coaxial electrospinning; core‐shell fibers; drug delivery; Drug Delivery Systems - methods; iron oxide nanoparticles; Magnetic Fields; Magnetic Iron Oxide Nanoparticles - chemistry; magnetic nanoparticles; Rats; reactive astrocytes; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - therapy; Transforming Growth Factor beta3 - administration & dosage; Transforming Growth Factor beta3 - metabolism; Transforming Growth Factor beta3 - pharmacology
• ISSN: 2701-0198; 2701-0198
• DOI: 10.1002/adbi.202300531

A spinal cord injury (SCI) compresses the spinal cord, killing neurons and glia at the injury site and resulting in prolonged inflammation and scarring that prevents regeneration. Astrocytes, the main glia in the spinal cord, become reactive following SCI and contribute to adverse outcomes. The anti‐inflammatory cytokine transforming growth factor beta 3 (TGFβ3) has been shown to mitigate astrocyte reactivity; however, the effects of prolonged TGFβ3 exposure on reactive astrocyte phenotype have not yet been explored. This study investigates whether magnetic core‐shell electrospun fibers can be used to alter the release rate of TGFβ3 using externally applied magnetic fields, with the eventual application of tailored drug delivery based on SCI severity. Magnetic core‐shell fibers are fabricated by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the shell and TGFβ3 into the core solution for coaxial electrospinning. Magnetic field stimulation increased the release rate of TGFβ3 from the fibers by 25% over 7 days and released TGFβ3 reduced gene expression of key astrocyte reactivity markers by at least twofold. This is the first study to magnetically deliver bioactive proteins from magnetic fibers and to assess the effect of sustained release of TGFβ3 on reactive astrocyte phenotype. There is a need for treatments that restore function after spinal cord injury. Here, magnetic core‐shell fibers are fabricated and loaded with a growth factor that reduces spinal cord astrocyte reactivity. Magnetic field stimulation increased the release rate of the growth factor, which could be used in future studies to non‐invasively tune delivery based on injury severity.